title: Apc1638N: a mouse model for familial adenomatous polyposis-associated desmoid tumors and cutaneous cysts.
abstract: OBJECTIVE
  Germline mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominant predisposition to the formation of multiple colorectal adenomas. Moreover, patients with FAP are at high risk of developing several extracolonic manifestations, including desmoids, cutaneous cysts, and tumors of the upper gastrointestinal tract. Although by definition desmoids are nonmalignant, because of their aggressive invasion of local structures, they represent one of the major causes of morbidity and mortality among patients with FAP.
  
  
  METHODS
  This study describes the histopathologic and molecular characterization of Apc1638N, a mouse model for the broad spectrum of extracolonic manifestations characteristic of FAP.
  
  
  RESULTS
  Heterozygous Apc+/Apc1638N animals develop fully penetrant and multifocal cutaneous follicular cysts and desmoid tumors in addition to attenuated polyposis of the upper gastrointestinal tract. Moreover, breeding of Apc+/Apc1638N mice in a p53-deficient background results in a dramatic seven-fold increase of the desmoid multiplicity.
  
  
  CONCLUSIONS
  Because of the attenuated nature of their intestinal phenotype, these mice survive longer than other murine models for Apc-driven tumorigenesis. Therefore, Apc1638N represents an ideal laboratory tool to test various therapeutic intervention strategies for the management of intestinal as well as extraintestinal tumors.
authors.affiliation: Medical Genetics Center South-West Netherlands, Department of Human Genetics, Leiden University.
authors.forename: R
authors.initials: R
authors.lastname: Smits
authors.forename: W
authors.initials: W
authors.lastname: van der Houven van Oordt
authors.forename: A
authors.initials: A
authors.lastname: Luz
authors.forename: C
authors.initials: C
authors.lastname: Zurcher
authors.forename: S
authors.initials: S
authors.lastname: Jagmohan-Changur
authors.forename: C
authors.initials: C
authors.lastname: Breukel
authors.forename: P M
authors.initials: PM
authors.lastname: Khan
authors.forename: R
authors.initials: R
authors.lastname: Fodde
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000150:complications* / Q000235:genetics; D017668:Age of Onset; D000818:Animals; D003560:Cysts / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018222:Desmoid Tumors / Q000209:etiology* / Q000473:pathology; D017491:Genes, APC / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000502:physiology; D009378:Neoplasms, Multiple Primary / Q000150:complications; D010641:Phenotype; D017678:Sex Distribution; D012871:Skin Diseases / Q000209:etiology* / Q000473:pathology